The invention pertains to a method for non-invasively and quantitatively evaluating the biomechanical status of bone at a specific locale or set of locales in vivo at a given time, where the biomechanical status is characterized quantitatively in terms of a set of elastic constants, bone strength and/or fracture risk.
In recent years, various attempts have been made to use diverse forms of energy to assess the condition of bone tissue in vivo. The primary means utilized presently involves the application of ionizing radiation, namely x-rays. These x-ray-based methods, while providing reasonable estimates of bone-mineral density, do not accurately distinguish individuals with respect to risk of osteoporotic bone fracture. This is due, in part at least, to the dependence of bone biomechanical properties on architectural or structural features, aspects, which are not captured in bone-mineral density measurements alone. In this regard, it should be noted that the architectural features refer primarily to the microstructure of the trabecular portion of a bone. It is this trabecular portion that provides the majority of the biomechanical strength and stiffness in many bones, which are involved in osteoporosis, such as the hip and vertebrae.
As noted, the primary means for assessing bone is to determine bone-mineral density with ionizing electromagnetic radiation, i.e. x-rays. A review of these radiation-based methods may be found in the article by Ott et al., in the Journal of Bone and Mineral Research, Vol. 2, pp. 201-210, 1987. These techniques all operate on the basic principle that the attenuation of an x-ray beam depends on the amount of bone present at a particular anatomical site in a subject's body, and that this attenuation (and therefore some information on the amount of bone present) can be evaluated. Several techniques exist for performing this type of densitometric measurement, such as single photon absortiometry (SPA), dual photon absortiometry (DPA), single energy x-ray absortiometry (SXA), dual energy x-ray absorptiometry (DXA), and quantitative computed tomography (QCT). A related but simpler bone density estimation method, known as radiographic densitometry (RA), has also been described (see, for example the 1991 publication by F. Cosman, B. Herrington, S. Himmelstein and R. Lindsay entitled "Radiographic Absorptiometry: A Simple Method for Determination of Bone Mass," in Osteoporosis International, Volume 2, pp. 34-38.) This technique, based on a plain radiograph, is applicable to appendicular sites only; it has mostly been applied to evaluation of the bone mineral density of the phalanges (fingers). It utilizes digital image processing to process a plain radiograph that was obtained with an aluminum alloy reference step wedge placed adjacent to the hand.
Acoustic techniques have also been utilized for non-invasive bone assessment, including for example, both ultrasonic and low-frequency vibrational methods. Although these techniques have the potential for providing a great deal of information on bone density and strength, they have not yet become widely used for in vivo bone assessment. Some reasons for this are that the techniques are highly sensitive to positioning and coupling of the acoustic transducers and are also affected by soft tissue overlying the bone.
Yoshida, et al., U.S. Pat. No. 5,426,709, discloses a plain x-ray measurement method and apparatus for evaluating bone mineral density of a bone, upon determination of quantity level of light that transmits through the x-ray film. The Yoshida, et al. device adjusts the light intensity level so that it is within a predetermined quantity range of light, in comparison to that which is transmitted through an aluminum step wedge. A temperature compensation for an output from the transmitting light detecting unit, i.e., a charge coupled device image sensor, is carried out by utilizing a light shielded output from the sensor.
U.S. Pat. No. 4,811,373 to Stein discloses a device to measure bone density. In the invention, Stein describes an x-ray tube operating at two voltages to generate a pencil beam, together with an integrating detector. The detector measures the patient-attenuated beam at the two energy levels (known commonly as dual energy x-ray absorptiometry) of the pencil beam. Calibration is accomplished by a digital computer on the basis of passing the pencil beam through a known bone-representing substance as the densitometer scans portion of the patient having bone and adjacent portions having only flesh.
Fletcher et al., in U.S. Pat. No. 3,996,471, disclose another dual energy x-ray absorptiometry method. In this invention, a target section of a living human body is irradiated with a beam of penetrative radiations of preselected energy to determine the attenuation of such beam with respect to the intensity of each of two radiations of different predetermined energy levels. The resulting measurements are then employed to determine bone mineral content.
Alvarez et al., in U.S. Pat. No. 4,029,963, disclose a method for decomposing an x-ray image into atomic-number-dependent and density-dependent projection information. The disclosed technique is based on the acquisition of x-ray images from the low and high energy regions, respectively.
Kaufman et al., U.S. Pat. Nos. 5,259,384 and 5,651,363, disclose method and apparatus for ultrasonically assessing bone tissue. In the first of the two Patents, a composite sine wave acoustic signal consisting of plural discrete frequencies within the ultrasonic frequency range to 2 MHz are used to obtain high signal-to-noise ratio of the experimental data. A polynomial regression of the frequency-dependent attenuation and group velocity is carried out, and a nonlinear estimation scheme is applied in an attempt to estimate the density, strength, and fracture risk of bone in vivo. In the second of the two Patents, a parametric modeling approach is used in a comparative analysis for assessment of bone properties.
U.S. Pat. No. 3,847,141 to Hoop discloses a device to measure bone density as a means of monitoring calcium content of the involved bone. A pair of opposed ultrasonic transducers is applied to opposite sides of a patient's finger, such that recurrent pulses transmitted via one transducer are "focused" on the bone, while the receiving response of the other transducer is similarly "focused" to receive pulses that have been transmitted through the bone. The circuitry is arranged such that filtered reception of one pulse triggers the next pulse transmission; the filtering is by way of a bandpass filter, passing components of received signals, only in the 25 to 125 kHz range; and the observed frequency of retriggering is said to be proportional to the calcium content of the bone.
Doemland, U.S. Pat. No. 4,754,763, discloses a noninvasive system for testing the integrity of a bone in vivo. He uses low-frequency mechanical vibrations to characterize the state of healing in a fractured bone. The frequency response is used to classify the stage of healing.
Cain et al., U.S. Pat. No. 5,368,044, applied a similar method, namely, low-frequency mechanical vibrations, to assess the state or stiffness of bone in vivo. The method evaluates the peak frequency response or a cross-correlation of the frequency vs. amplitude response.
Cheng et al., U.S. Pat. No. 5,772,592, disclosed a method for diagnosing and monitoring osteoporosis, using volumetric bone density and cross-sectional area information in a patient.
Wehrli et al., U.S. Pat. No. 5,247,934, disclosed a method for diagnosing osteoporosis with magnetic resonance imaging. In their approach, a measure of trabecular thickness and bone perimeter, determined from magnetic resonance imaging, are used together to assess the condition of trabecular bone at the site of interest.
The prior art, exemplified by the references that have been briefly discussed, have had little success in providing an accurate determination of the biomechanical state of a bone in a living body. They have focussed primarily on x-ray bone densitometric techniques, such as dual energy methods, which provide measures of bone-mineral density only, which is limited in terms of its relation to bone elasticity, strength and fracture risk. On the other hand, acoustic (low-frequency vibrational or ultrasonic) means have not yet produced an accurate practical method for clinical bone assessment either.
Of great utility in the field of bone assessment would be a technique which could provide accurate assessment of the biomechanical properties of bone in vivo, but without significant additional complexity as compared to that associated with x-ray bone densitometers, such as offered by dual energy x-ray absorptiometry.